Chemical strategies to overcome resistance against targeted anticancer therapeutics.

Nature Chemical Biology
Rudolf Pisa, Tarun M Kapoor

Abstract

Emergence of resistance is a major factor limiting the efficacy of molecularly targeted anticancer drugs. Understanding the specific mutations, or other genetic or cellular changes, that confer drug resistance can help in the development of therapeutic strategies with improved efficacies. Here, we outline recent progress in understanding chemotype-specific mechanisms of resistance and present chemical strategies, such as designing drugs with distinct binding modes or using proteolysis targeting chimeras, to overcome resistance. We also discuss how targeting multiple binding sites with bifunctional inhibitors or identifying collateral sensitivity profiles can be exploited to limit the emergence of resistance. Finally, we highlight how incorporating analyses of resistance early in drug development can help with the design and evaluation of therapeutics that can have long-term benefits for patients.

References

Jul 5, 2001·Proceedings of the National Academy of Sciences of the United States of America·K M SakamotoR J Deshaies
May 11, 2002·Science·Jung-Hyun MinNikola P Pavletich
Jul 3, 2002·Nature Reviews. Cancer·Igor Vivanco, Charles L Sawyers
Jul 18, 2002·Nature Reviews. Drug Discovery·Renaud CapdevilleAlex Matter
Mar 5, 2004·The New England Journal of Medicine·François Clavel, Allan J Hance
Feb 25, 2005·The New England Journal of Medicine·Susumu KobayashiBalázs Halmos
Apr 20, 2006·Antiviral Research·Douglas D Richman
Jul 5, 2006·Quarterly Reviews of Biophysics·George M Whitesides, Vijay M Krishnamurthy
Apr 6, 2007·Nature·Remy ChaitRoy Kishony
Jan 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Cai-Hong YunMichael J Eck
May 13, 2008·Nature Reviews. Cancer·Klaus Strebhardt, Axel Ullrich
Jan 31, 2009·Nature Reviews. Drug Discovery·Jia JiaYu Zong Chen
Dec 25, 2009·Nature·Wenjun ZhouPasi A Jänne
Mar 13, 2010·Science·Takumi ItoHiroshi Handa
Apr 24, 2010·FEMS Microbiology Reviews·Merijn L M SalverdaMiriam Barlow
Oct 29, 2010·The New England Journal of Medicine·Young Lim ChoiUNKNOWN ALK Lung Cancer Study Group
Nov 26, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Thomas O'HareBrian J Druker
Apr 2, 2011·Nature Reviews. Drug Discovery·Juswinder SinghAdrian Whitty
Jan 13, 2012·Nature·Jinghui ZhangMichael A Dyer
Jan 27, 2012·Science Translational Medicine·Ryohei KatayamaJeffrey A Engelman
Feb 14, 2012·Nature Chemical Biology·Sarah A WackerTarun M Kapoor
Apr 3, 2013·Journal of the American Chemical Society·Eugene F DouglassDavid A Spiegel
Sep 27, 2013·Science Translational Medicine·Lejla Imamovic, Morten O A Sommer
Mar 4, 2014·Nature Communications·Diwakar ShuklaVijay S Pande
Mar 29, 2014·Cancer Discovery·Luc FribouletJeffrey A Engelman
May 30, 2014·The New England Journal of Medicine·Richard R FurmanY Lynn Wang
Jun 16, 2014·Nature Chemical Biology·Corynn KasapTarun M Kapoor
Jul 22, 2014·Nature·Eric S FischerNicolas H Thomä
Aug 12, 2014·Nature Structural & Molecular Biology·Philip P ChamberlainBrian E Cathers
Sep 5, 2014·Cancer Discovery·Brian D CromptonKimberly Stegmaier
Oct 9, 2014·The New England Journal of Medicine·Nikhil WagleJochen H Lorch
Mar 26, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Bristi BasuUdai Banerji

❮ Previous
Next ❯

Citations

Aug 10, 2020·Molecular & Cellular Proteomics : MCP·Xuepei ZhangRoman A Zubarev
Jan 12, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Chang DuChang-Ming Dong
Mar 31, 2021·Nature Structural & Molecular Biology·Tommaso CupidoTarun M Kapoor
May 19, 2021·Nature Reviews. Cancer·Shuai ZhaoGang Greg Wang
Sep 16, 2021·ACS Infectious Diseases·Barbara ForteIan H Gilbert

❮ Previous
Next ❯

Methods Mentioned

BETA
ubiquitination
xenograft
RNA-seq

Software Mentioned

RADD
DrugTargetSeqR
PROTAC

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.